38 results about "METHOXYAMINE HYDROCHLORIDE" patented technology

The invention provides a method for synthesizing methoxyamine hydrochloride and includes the following steps: ethyl acetate and hydroxylamine hydrochloride are added into a reaction vessel and 10 to 30 percent of sodium hydroxide solution is instilled for oximation reaction; then dimethyl sulfate is instilled, and at the same time sodium hydroxide solution with the mass fractions of 10 to 30 percent is instilled for methylation reaction; cold water is added after the temperature is decreased and a halohydrocarbon solvent is adopted for extraction; pressure is reduced under the temperature of 30 to 50 DEG C to recover the halohydrocarbon solvent and the product obtained is added into inorganic acid solution for hydrolysis reaction; after the hydrolysis is over, hydrochloride is used to obtain the product methoxyamine hydrochloride. The synthetic method which is simple improves the operation environment and increases the yield ratio.

The invention discloses a bufalin glycosylation derivative and a preparation method and application thereof in preparation of anti-tumour medicaments. The structure of the bufalin glycosylation derivative is shown in a formula I or formula II. The synthesis method of the bufalin glycosylation derivative comprises the following steps of: oxidizing bufalin into a ketone-form derivative by pyridinium chloropyridine hydrochloride; then performing a nucleophilic addition reaction with methoxyamine hydrochloride; removing monomolecular water to generate an oxime-form intermediate; enabling the oxime-form intermediate to react with a tert-butylamine borane hydrochloride compound to generate alpha-configuration aglycone and beta-configuration aglycone; and finally enabling the aglycones of two configurations to react with reducing sugar respectively to generate the bufalin glycosylation derivative. According to the method disclosed by the invention, bufalin is modified to be the glycosylation derivative thereof, and the water solubility can be improved while the anti-tumour activity is kept and enhanced; and moreover, in-vivo experiments prove that the toxic and side effects of the bufalin glycosylation derivative disclosed by the invention on normal cells are reduced compared with those of a parent compound of bufalin.

The invention relates to the technical field of compound synthesis methods, particularly a method for coproducing vasoxine hydrochloride and N,O-dimethylhydroxylamine hydrochloride. The method comprises the following steps: carrying out methylation reaction on hydroxylamine salt under alkaline conditions by using a methylating agent to obtain a reaction solution containing vasoxine and N,O-dimethylhydroxylamine, rectifying to separate a vasoxine bottom solution and an N,O-dimethylhydroxylamine crude distillate, respectively adding hydrochloric acid for salification, concentrating and crystallizing under reduced pressure, cooling, carrying out vacuum filtration, recrystallizing with water or methanol, and drying to obtain the vasoxine hydrochloride product and N,O-dimethylhydroxylamine hydrochloride product. The method has the advantages of simple and reliable technique, high product quality, high total yield and low comprehensive cost, and is more friendly to the environment and suitable for industrial production.

The invention belongs to the technical field of fluorine compound preparation, in particular to a 3-bromofluorenone preparation method. The 3-bromofluorenone preparation method comprises the following steps: A, oximation reaction: adding fluorenone and methoxamine hydrochloride into a solvent, performing oximation reaction, and performing reaction quenching to obtain fluorenone methoxy oxime; B, bromination reaction: adding a catalyst, bromine and the fluorenone methoxy oxime obtained in the step A into the solvent, and performing reaction quenching to obtain a bromide product; C, hydrolysis reaction: adding the bromide product obtained in the step B into the solvent, and performing hydrolysis reaction at the temperature of 50 to 100 DEG C to obtain 3-bromofluorenone. The preparation method is simple and low in cost, the obtained 3-bromofluorenone is high in yield and high in purity, the reaction conditions are mild, and the 3-bromofluorenone is suitable for industrial production.

The invention relates to the technical field of compound synthesis methods, and discloses a method for synthesizing methoxyamine hydrochloride. The method comprises the following steps: adding water, sodium hydroxide, diacetylmonoxime and a phase transfer catalyst into a reaction kettle; after cooling, adding a methylation reagent; conducting standing for layering to obtain an organic layer, a water layer and a distilled water layer, collecting distillate, combining an oil layer and the distillate, and adding hydrochloric acid for mixing to obtain a mixed solution; feeding and rectifying the mixed solution from the middle of a rectifying column, recovering butanone and methanol at the top of the column, recovering a methoxyamine hydrochloride solution at the bottom of the column, and carrying out evaporating and dehydrating to obtain a concentrated solution; and cleaning a reaction kettle, wherein a stirring mechanism and a cleaning mechanism are arranged in the reaction kettle, the cleaning mechanism comprises a scraping plate, a spraying pipe, a lifting assembly and a rotating assembly, a water inlet pipe and a cleaning nozzle are connected to the spraying pipe, the reaction kettle comprises a kettle body and a kettle cover, the water outlet end of the cleaning nozzle faces the side wall of the kettle body, and the scraping plate is attached to the side wall of the kettle body. The method has the effect of conveniently cleaning residues on the side wall of the kettle body.

The present application discloses a method for preparing methoxyamine, which at least includes: contacting a raw material gas containing methyl nitrite and a reducing agent with a reduction reaction catalyst in a reactor to perform a reduction reaction to obtain methoxyamine. The method can fully utilize the important intermediate methyl nitrite in the coal-to-ethylene glycol process, and the conversion rate of the methyl nitrite is high. The present application also provides a preparation method of methoxyamine hydrochloride obtained by the above method as raw material.

The invention discloses a preparation method of gemifloxacin side chain compound. The preparation method comprises the following steps: S1, 1-N-tert-butoxycarbonyl-4-cyano-3-pyrrolidone reacts with methoxylamine hydrochloride to obtain the compound shown in formula (V); S2, in an inert In the atmosphere, at a temperature of 10-50°C and in the presence of palladium carbon, the compound shown in formula (Ⅴ) is subjected to a hydrogenation reduction reaction for 1-3 hours under a hydrogen atmosphere of 0.1-0.5Mpa; then Boc anhydride is added, and the Continue the hydrogenation reduction reaction at 10-50°C and 0.1-0.5Mpa for 4-8 hours to obtain the compound shown in formula (VI); S3, the compound shown in formula (VI) reacts with an acid to remove the protecting group to obtain Gemifloxacin side chain compound represented by formula (I). The preparation method of the present invention has simple process, very mild reaction conditions, and is easy to realize; (2) the raw material price is low, and the cost is low; (3) a new and effective synthesis process route of gemifloxacin side chain is created.

The invention provides a preparation method of a zabofloxacin intermediate. The method comprises: reacting ethyl glycinate hydrochloride with acrylonitrile under catalysis of a base to form an intermediate I; then reacting the intermediate I with Boc anhydride under the function of a strong base to generate an intermediate III; reacting the intermediate III, the methoxyamine hydrochloride and formaldehyde to generate an intermediate IV; and then preparing the zabofloxacin intermediate by reacting the intermediate IV with methanesulfonyl chloride, performing reduction with sodium borohydride, and other steps. The zabofloxacin intermediate is prepared through nine steps with a high yield and high quality by the method, the material adding amount reaches the level of hundreds of grams, and the method is suitable for industrial production.

The invention discloses a chemical derivation-based detection method for hemolymph metabolin of migratory locust, and relates to the field of animal ecology and analytical chemistry. The detection method specifically comprises the following steps of: taking hemolymph, deproteinizing by adding ethanol-acetonitrile mixed solvent, supersonically extracting, and centrifuging at a high speed to obtain metabolin extracting solution; drying the extracting solution by means of pressure reduction, adding methoxamine hydrochloride-pyridine solution, supersonically dissolving, blending by means of vortex, and deriving in an oximation way in a constant-temperature water bath; adding N-methyl-N-trimethylsilane-trifluoroacetamide reagent, blending by means of vortex, and deriving in an alkylation way in the constant-temperature water bath; and adding methyl oleate-normal heptane solution to compensate the volume, blending by means of vortex, and analyzing by a spare gas chromatography-mass spectra coupling technique. The detection method provided by the invention is convenient, high-efficiency, mild in reaction conditions, good in repeatability, wide in metabolin coverage, suitable for developing the multi-center and large-sample research, and capable of providing help for knowing the biological law of various migratory locust variations and the occurrence mechanism of the locust plague.

The present invention provides a method for preparing relugoli intermediate compound 8, said method comprising the following steps: (a) reacting compound 2 with N,N'-carbonyldiimidazole to obtain compound 3; (b) compound 3 React with 2,6-difluorobenzyl chloride to give compound 4; (c) react compound 4 with 3-amino-6-methoxypyridazine to give compound 5; (d) react compound 5 with N,N'-carbonyl Diimidazole reacts to obtain compound 6; (e) compound 6 reacts with N-bromosuccinimide and azobisisobutyronitrile to obtain compound 7; (f) compound 7 reacts with dimethylamine hydrochloride, Compound 8 was obtained. The present invention also provides a method for preparing relugoli, said method comprising the following steps: (g) reacting compound 8 prepared by the above method with hydrogen under a catalyst to obtain compound 9; (h) compound 9 and N , N'‑carbonyldiimidazole and methoxylamine hydrochloride were reacted to obtain relugoli. The method for preparing relugoli provided by the present invention adopts the route of first ring closure and then coupling, which has simpler operation, fewer side reactions, mild reaction conditions, high yield and purity, easy purification of the product, and is suitable for commercial scale production.

The present invention relates to the field of chemical industry. The present invention is a method for refining methoxyamine hydrochloride. First, the volatile organic matter and reaction raw materials in the reaction liquid are rectified and removed by rectification, and then concentrated by a concentration tower and then added The organic solvent causes the inorganic salt to precipitate, and the inorganic salt in the kettle liquid is removed by filtration; what this method uses is a kind of hydrophilic polysulfone microporous filtration membrane, which has good filtration effect and filtration efficiency, and does not affect the process of the whole process. Continuity; the present invention uses the principle of the different solubility of methoxyamine hydrochloride and inorganic salts in organic solvents to precipitate inorganic salts by adding organic solvents, and then achieve the purpose of removing inorganic salts; organic solvents of the present invention can be recycled , do not increase the material cost of production, do not increase the treatment capacity of the three wastes, and the methoxyamine hydrochloride purified by the method of the present invention has higher purity, which improves product quality and market competitiveness.

The invention belongs to the field of synthesis of fine chemical intermediates, and discloses a method for preparing methoxyamine hydrochloride by using a microreactor. It is specifically divided into: the preparation of acetaminolamine, the preparation of acetylmethoxamine and the preparation of methoxylamine hydrochloride, wherein the preparation process of acetylhydroxylamine and acetylmethoxylamine is carried out in a microreactor. Specifically, the hydroxylamine hydrochloride solution, ethyl acetate and lye are pumped into the microchannel reaction module A, and after being mixed in the microchannel, they are pumped into the microchannel reaction module B again with dimethyl sulfate and lye, and collected after the mixed reaction. After hydrolysis, distillation, neutralization, salt formation, concentration and other processes, methoxyamine hydrochloride is obtained. Compared with the prior art, the invention effectively improves the yield of methoxyamine hydrochloride by utilizing the microreactor, reduces the generation of three wastes, shortens the reaction time and reduces the production cost.

The invention discloses a benzenesulfonylation reagent. The structure of the benzenesulfonylation reagent is shown as formula I in the specification, wherein R is a benzene ring connected with 0-5 substituents, and the substituents on the benzene ring are chlorine atoms, fluorine atoms, methyl groups or tert-butyl groups independently. The invention further discloses a preparation method and an application of the benzenesulfonylation reagent. The benzenesulfonylation reagent is prepared from methoxyamine hydrochloride and benzenesulfonyl chloride or a benzenesulfonyl chloride derivative through two steps of reactions, raw materials are cheap, a preparation process is simple, reaction conditions are mild, few side effects are produced, only extraction and simple column chromatographic purification are needed for aftertreatment, and the yield is high. The benzenesulfonylation reagent has higher benzenesulfonylation activity, benzenesulfonylation reaction conditions are mild, a reaction substrate range is wider, compounds such as alcohol, phenol, naphthol, thiophenol and the like can be subjected to a benzenesulfonylation reaction in presence of acetonitrile neutralized potassium carbonate, and -C1 does not exist on the benzenesulfonylation reagent, so that HCl gas with pungent odor cannot be emitted during application.

The invention discloses a synthesis method of 4-allyl-3,5-disubstituted isoxazole, belonging to the technical field of organic synthesis. The synthesis method is as follows: in the reactor, add acetylene ketoxime ether substrate, 3-bromopropene, palladium catalyst, additive and solvent, stir and react at 70-80°C, and the reaction product is separated and purified to obtain 4-allyl -3,5-disubstituted isoxazoles. In the method of the present invention, a series of acetylenic ketone oxime ethers are obtained by reacting the product obtained through Sonogashira coupling of simple and easy-to-obtain acyl chlorides and alkynes with methoxyamine hydrochloride, the reaction conditions are mild, and there is no pollution to the environment. Potentially functional 4-allyl-3,5-disubstituted isoxazole compounds, the method is innovative and atom-economical, mild conditions, safe operation, and can be scaled up to 5 g scale without affecting the yield Therefore, it has potential practical value.

The invention provides a preparation method of a zabofloxacin intermediate. The method comprises: reacting ethyl glycinate hydrochloride with acrylonitrile under catalysis of a base to form an intermediate I; then reacting the intermediate I with Boc anhydride under the function of a strong base to generate an intermediate III; reacting the intermediate III, the methoxyamine hydrochloride and formaldehyde to generate an intermediate IV; and then preparing the zabofloxacin intermediate by reacting the intermediate IV with methanesulfonyl chloride, performing reduction with sodium borohydride, and other steps. The zabofloxacin intermediate is prepared through nine steps with a high yield and high quality by the method, the material adding amount reaches the level of hundreds of grams, and the method is suitable for industrial production.

The invention discloses a preparation method of a gemifloxacin side chain compound. The preparation method comprises the following steps: S1, carrying out a reaction on 1-N-tert-butyloxycarbonyl-4-cyano-3-pyrrolidone and methoxyamine hydrochloride to obtain a compound as shown in a formula (V); S2, in an inert atmosphere, at a temperature of 10-50 DEG C, in the presence of palladium on carbon, and in a hydrogen atmosphere of 0.1-0.5 Mpa, carrying out a hydrogenation reduction reaction on the compound as shown in the formula (V) for 1-3 h; adding Boc anhydride, continuing the hydrogenation reduction reaction for 4-8 h under the conditions of 10-50 DEG C and 0.1-0.5 Mpa, and obtaining a compound shown in the formula VI; S3, enabling the compound shown in the formula VI to react with acid to remove the protecting group, and obtaining the gemifloxacin side chain compound shown in the formula I. The preparation method disclosed by the invention is simple in process, very mild in reaction condition and very easy to implement; (2) the raw materials are low in price and cost; (3) a novel and effective gemifloxacin side chain synthesis process route is created.